What are angiotensin-converting enzyme inhibitors? How do they interact with other drugs?

Quick Answer
Medications that block the conversion of a naturally occurring substance, angiotensin, to a more active form.
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Effect: Possible Harmful Interaction

Arginine is an amino acid that has been used to improve immunity in hospitalized persons and used for many other conditions. Based on experience with intravenous arginine, it is possible that the use of high-dose oral arginine might alter potassium levels in the body, especially in people with severe liver disease. This is a potential concern for persons who take ACE inhibitors.


Effect: Possible Harmful Interaction

Licorice root, a member of the pea family, has been used since ancient times as both food and medicine. Whole licorice (Glycyrrhiza glabra or G. uralensis) can cause sodium retention and increase blood pressure, thus counteracting the intended effects of ACE inhibitors. An often unrecognized source of licorice is chewing tobacco. A special form of licorice known as DGL (deglycyrrhizinated licorice) is a deliberately altered form of the herb that should not cause these problems.


Effect: Possible Harmful Interaction

ACE inhibitors cause the body to retain more potassium than usual. This could raise blood levels of potassium too high, a condition called hyperkalemia, which can be dangerous. Depending on how high a person’s potassium levels, the symptoms could include irregular heart rhythm, muscle weakness, nausea, vomiting, irritability, and diarrhea. Persons taking any ACE inhibitors should not take potassium supplements except on medical advice.

Because ingesting more potassium makes the problem worse, it is important to be aware of the various sources of extra potassium. Besides potassium supplements, sources include high-potassium diets, salt substitutes containing potassium, and potassium-sparing diuretics (diuretics that cause the body to retain potassium).

Dong Quai, St. John’s wort

Effect: Possible Harmful Interaction

St. John’s wort (Hypericum perforatum) is primarily used to treat mild to moderate depression. The herb dong quai (Angelica sinensis) is often recommended for menstrual disorders such as dysmenorrhea, PMS, and irregular menstruation.

ACE inhibitors have been reported to cause increased sensitivity to the sun, amplifying the risk of sunburn or skin rash. Because St. John’s wort and dong quai may also cause this problem, taking these herbal supplements during treatment with ACE inhibitors might add to this risk. It may be a good idea to wear sunscreen or protective clothing during sun exposure if also taking one of these herbs while using an ACE inhibitor.


Effect: Possible Benefits and Risks

Persons taking ACE inhibitors frequently develop a dry cough as a side effect. One study suggests that iron supplementation can alleviate this symptom. In this four-week, double-blind, placebo-controlled trial of nineteen persons, use of iron as ferrous sulfate significantly reduced cough symptoms compared with placebo.

One should keep in mind that it is not healthy to get too much iron. For this reason, it is recommended that one seek medical advice before starting iron supplements. However, iron supplements can interfere with the absorption of captopril and perhaps other ACE inhibitors. Iron appears to bind with captopril, resulting in a compound that the body cannot absorb. This also impairs iron absorption. To minimize any potential problems, one should take iron supplements and ACE inhibitors two to three hours apart.


Effect: Supplementation Possibly Helpful

ACE inhibitors may cause zinc depletion. The ACE inhibitors captopril and enalapril attach to the trace mineral zinc. Because zinc in this bound form cannot replace the zinc that the body uses to meet its normal needs, a gradual loss of zinc from body tissues may result. Continued drug therapy could lead to zinc deficiency.

It has been suggested, though not proven, that zinc deficiency might account for some of the side effects seen with ACE inhibitors. These side effects include taste disturbances, poor appetite, and skin numbness or tingling.

Whether zinc supplementation will prevent ACE inhibitor-induced zinc deficiency has not been examined, so it seems that taking extra zinc could help. Generally, zinc supplements should also contain copper to prevent zinc-induced copper deficiency.


AHFS Drug Information. Bethesda, Md.: American Society of Health-System Pharmacists, 2000.

Golik, A., et al. “Effects of Captopril and Enalapril on Zinc Metabolism in Hypertensive Patients.” Journal of the American College of Nutrition 17 (1998): 75-80.

Good, C. B., L. McDermott, and B. McCloskey. “Diet and Serum Potassium in Patients on ACE Inhibitors.” Journal of the American Medical Association 274 (1995): 538.

Lee, S. C., et al. “Iron Supplementation Inhibits Cough Associated with ACE Inhibitors.” Hypertension 38 (2001): 166-170.